The purpose of this project is to use the mouse Beta-globin system as a model for eventual gene therapy of Beta-thalassemia in humans. We have used recombinant DNA technology to study two areas important for proper regulation of a gene introduced into cells: a) the effect of DNA enhancing sequences on the mouse Beta-globin promoter, both in tissue culture cells and in mice; and b) possible mechanism of enhancer function. To test the effect of known enhancers and to look for new enhancers, various plasmids, called expression vectors, have been constructed. Attempts to isolate proteins which influence enhancer activity are also underway.